Project Summary/Abstract People living in the United States with a retinal disease account for ~12 million. Visual disturbances are some of the most common, bothersome and debilitating consequences of retinal pathology, that can result in blindness. Studies of retinal diseases in vivo offer a plethora of information that is used to guide treatments, interventions, and eventually prevention. Currently, the structural consequences of these diseases can be assessed with unprecedented resolution at the cellular level, and over the past few decades, this information led to a better understanding of their natural history. The manifestation of a disease always has a structural and a functional component, and to date, there are no methods for measuring retinal function objectively at a high spatial resolution and high spatial accuracy. While several methods have been successfully developed for correcting for eye movements in retinal imaging modalities, little effort has been dedicated on correcting for eye movements in retinal functional modalities, like the multifocal electroretinogram (ERG). With this proposal, we aim to develop a system using eye-tracking technology and electrophysiological equipment to avoid spatial averaging during ERG recordings and at the same time achieve high retinal spatial accuracy. We will interface an eye-tracker with a display to create a gaze-contingent display while we record ERGs and eye-movements at the same time. By having eye movement data throughout the recording, we will also be able to correct for gaze location offline. The experiments we propose will also test the spatial resolution limits we can achieve with electrophysiological means, and we will use these data to create a high-resolution, high-accuracy functional map of the retina. The developed methods could then be used in basic and clinical research for a plethora of retinal diseases, or for answering neuroscience questions. The high resolution and accuracy ERGs can be performed to study disease progression at specific retinal locations, to examine the disease front like the geographic atrophy in advanced dry age-related macular degeneration and other debilitating retinal pathologies. This proposal addresses needs identified in the NEI Publication ?Vision Research: Needs, Gaps, and Opportunities?: ?Characterize the macula and perifoveal regions of the retina to better understand the predilection of the macula for disease.?